CA1163922A - Method for stabilizing plasminogen - Google Patents
Method for stabilizing plasminogenInfo
- Publication number
- CA1163922A CA1163922A CA000368755A CA368755A CA1163922A CA 1163922 A CA1163922 A CA 1163922A CA 000368755 A CA000368755 A CA 000368755A CA 368755 A CA368755 A CA 368755A CA 1163922 A CA1163922 A CA 1163922A
- Authority
- CA
- Canada
- Prior art keywords
- plasminogen
- salt
- physiologically acceptable
- inorganic salt
- acceptable inorganic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 102000013566 Plasminogen Human genes 0.000 title claims abstract description 57
- 108010051456 Plasminogen Proteins 0.000 title claims abstract description 57
- 238000000034 method Methods 0.000 title claims abstract description 29
- 230000000087 stabilizing effect Effects 0.000 title claims abstract description 6
- 239000007864 aqueous solution Substances 0.000 claims abstract description 19
- 229910017053 inorganic salt Inorganic materials 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 238000002360 preparation method Methods 0.000 claims description 24
- 239000000243 solution Substances 0.000 claims description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 12
- 238000010438 heat treatment Methods 0.000 claims description 12
- 210000002381 plasma Anatomy 0.000 claims description 9
- 235000002639 sodium chloride Nutrition 0.000 claims description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- -1 alkali metal salt Chemical class 0.000 claims description 7
- 239000011780 sodium chloride Substances 0.000 claims description 6
- 235000011007 phosphoric acid Nutrition 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
- 150000003863 ammonium salts Chemical class 0.000 claims description 4
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 4
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 4
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 4
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 4
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims description 4
- 235000019797 dipotassium phosphate Nutrition 0.000 claims description 4
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 4
- 239000001103 potassium chloride Substances 0.000 claims description 4
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 4
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 4
- 230000029087 digestion Effects 0.000 claims description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 6
- 239000007836 KH2PO4 Substances 0.000 claims 3
- 229910004835 Na2B4O7 Inorganic materials 0.000 claims 3
- 239000007832 Na2SO4 Substances 0.000 claims 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 3
- 239000004327 boric acid Substances 0.000 claims 3
- 229910000397 disodium phosphate Inorganic materials 0.000 claims 3
- UQGFMSUEHSUPRD-UHFFFAOYSA-N disodium;3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane Chemical compound [Na+].[Na+].O1B([O-])OB2OB([O-])OB1O2 UQGFMSUEHSUPRD-UHFFFAOYSA-N 0.000 claims 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims 3
- 235000019796 monopotassium phosphate Nutrition 0.000 claims 3
- 229960004838 phosphoric acid Drugs 0.000 claims 3
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 claims 3
- 229910052938 sodium sulfate Inorganic materials 0.000 claims 3
- 235000011152 sodium sulphate Nutrition 0.000 claims 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims 2
- 235000019800 disodium phosphate Nutrition 0.000 claims 2
- 235000011147 magnesium chloride Nutrition 0.000 claims 1
- 235000011164 potassium chloride Nutrition 0.000 claims 1
- 239000003381 stabilizer Substances 0.000 description 19
- 230000000694 effects Effects 0.000 description 14
- 238000011282 treatment Methods 0.000 description 7
- 238000004108 freeze drying Methods 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 208000006454 hepatitis Diseases 0.000 description 3
- 231100000283 hepatitis Toxicity 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108010023197 Streptokinase Proteins 0.000 description 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 2
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 235000010338 boric acid Nutrition 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 229960005202 streptokinase Drugs 0.000 description 2
- 229960005356 urokinase Drugs 0.000 description 2
- XDVOLDOITVSJGL-UHFFFAOYSA-N 3,7-dihydroxy-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane Chemical compound O1B(O)OB2OB(O)OB1O2 XDVOLDOITVSJGL-UHFFFAOYSA-N 0.000 description 1
- ODPOAESBSUKMHD-UHFFFAOYSA-L 6,7-dihydrodipyrido[1,2-b:1',2'-e]pyrazine-5,8-diium;dibromide Chemical compound [Br-].[Br-].C1=CC=[N+]2CC[N+]3=CC=CC=C3C2=C1 ODPOAESBSUKMHD-UHFFFAOYSA-L 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 239000005630 Diquat Substances 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 229960002645 boric acid Drugs 0.000 description 1
- 125000005619 boric acid group Chemical class 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- VGTPKLINSHNZRD-UHFFFAOYSA-N oxoborinic acid Chemical compound OB=O VGTPKLINSHNZRD-UHFFFAOYSA-N 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 238000001470 plasma protein fractionation Methods 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229940005657 pyrophosphoric acid Drugs 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229960005480 sodium caprylate Drugs 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6435—Plasmin (3.4.21.7), i.e. fibrinolysin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21007—Plasmin (3.4.21.7), i.e. fibrinolysin
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP807280A JPS56106594A (en) | 1980-01-25 | 1980-01-25 | Stabilizing method of plasminogen |
JP8072/80 | 1980-01-25 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1163922A true CA1163922A (en) | 1984-03-20 |
Family
ID=11683132
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA000368755A Expired CA1163922A (en) | 1980-01-25 | 1981-01-19 | Method for stabilizing plasminogen |
Country Status (3)
Country | Link |
---|---|
US (1) | US4361652A (ko) |
JP (1) | JPS56106594A (ko) |
CA (1) | CA1163922A (ko) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3119157A1 (de) * | 1981-05-14 | 1982-12-09 | Behringwerke Ag, 3550 Marburg | Verfahren zur herstellung von und danach hergestelltes plasminogen |
US4782023A (en) * | 1984-02-03 | 1988-11-01 | Abbott Laboratories | Stabilized horseradish peroxidase conjugate composition |
US4891311A (en) * | 1984-02-03 | 1990-01-02 | Abbott Laboratories | Stabilized enzyme conjugate composition |
JPH0725696B2 (ja) * | 1986-05-29 | 1995-03-22 | 株式会社ミドリ十字 | プラスミノ−ゲンの安定化方法 |
JP2545231B2 (ja) * | 1987-06-18 | 1996-10-16 | 日本ケミカルリサ−チ株式会社 | ウロキナ−ゼの加熱による低分子化抑制法 |
US5879923A (en) * | 1995-06-26 | 1999-03-09 | Daiichi Pure Chemicals Co., Ltd. | Stable plasmin solution |
US6964764B2 (en) * | 1999-11-13 | 2005-11-15 | Talecris Biotherapeutics, Inc. | Method of thrombolysis by local delivery of reversibly inactivated acidified plasmin |
US7544500B2 (en) * | 1999-11-13 | 2009-06-09 | Talecris Biotherapeutics, Inc. | Process for the production of a reversibly inactive acidified plasmin composition |
US6969515B2 (en) | 1999-11-13 | 2005-11-29 | Talecris Biotherapeutics, Inc. | Method of thrombolysis by local delivery of reversibly inactivated acidified plasmin |
US6355243B1 (en) | 1999-11-13 | 2002-03-12 | Bayer Corporation | Method of thrombolysis by local delivery of active plasmin |
JP2005287226A (ja) * | 2004-03-30 | 2005-10-13 | Tamura Seisakusho Co Ltd | スイッチング電源の同期回路およびスイッチング電源 |
DK1786273T3 (en) | 2004-08-20 | 2019-02-18 | Prometic Biosciences Ltd | SEQUENTIAL PROTEIN INSULATION AND PURIFICATION PLANS WITH AFFINITY CHROMATOGRAPHY |
CA2726908C (en) * | 2008-06-04 | 2017-01-24 | Talecris Biotherapeutics, Inc. | Composition, method, and kit for preparing plasmin |
PL2403865T3 (pl) | 2009-03-03 | 2016-01-29 | Grifols Therapeutics Inc | Sposoby wytwarzania plazminogenu |
WO2014150022A1 (en) | 2013-03-15 | 2014-09-25 | Grain Processing Corporation | Preparation of malto-oligosaccharides |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2897123A (en) * | 1956-09-21 | 1959-07-28 | Ortho Pharma Corp | Plasminogen sterilization |
US2923665A (en) * | 1956-11-07 | 1960-02-02 | American Cyanamid Co | Processes for preparing human plasminogen from human placenta sources |
US3227626A (en) * | 1961-09-18 | 1966-01-04 | Merck & Co Inc | Plasminogen heat sterilization |
US3865692A (en) * | 1974-01-11 | 1975-02-11 | Abbott Lab | Method for making highly potent plasminogen |
-
1980
- 1980-01-25 JP JP807280A patent/JPS56106594A/ja active Granted
-
1981
- 1981-01-16 US US06/225,531 patent/US4361652A/en not_active Expired - Lifetime
- 1981-01-19 CA CA000368755A patent/CA1163922A/en not_active Expired
Also Published As
Publication number | Publication date |
---|---|
JPS6235756B2 (ko) | 1987-08-04 |
JPS56106594A (en) | 1981-08-24 |
US4361652A (en) | 1982-11-30 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
MKEX | Expiry |